We propose to study the role of TRH (Thyrotropin Releasing Hormone) and the mechanisms regulating the activity of TRH in the central nervous system. We will be specifically concerned with mechanisms of inactivation. Two TRH inactivating enzymes have been described from studies on homogenates of mammalian brain: a deamidating enzyme and a pyroglutamate cleaving enzyme. Our objective in these pilot studies is to characterize and localize these enzymatic activities. We will determine conditions sufficient for their stability and procedures that permit each to be assayed without interference from the other. Then we will localize these activities in brain by determining the Km and Vmax for each in various brain regions. These experiments will set the stage for the purification of these enzymes and for their use in the study of TRH function. Localization of the TRH inactivating enzymes will help to identify the domains of action of TRH. The ability to manage the activity of these enzymes will lead to the ability to regulate TRH concentration in experimental and clinical work. TRH has a potential role in the diagnosis and treatment of mental illness. Our long term objectives are to contribute to the understanding and treatment of psychosis.